The effect of new medical treatment for hereditary retinal degeneration based on its molecular pathogenesis

本研究项目的目的是研究遗传性视网膜变性（即视网膜色素变性）的相关基因，并根据分子遗传学分析获得的分子发病机制的发现，研究这些疾病的新医学治疗的可能性。关于第一点，即色素性视网膜炎及相关疾病的分子遗传分析，我们首次报道了GCAP2基因是色素性视网膜炎的负责基因之一，这是基于我们在三个独立的日本家庭的受影响成员中发现了GCAP2基因的相同突变（Sato, Nakazawa, et al.,2005）。我们关注该基因作为色素性视网膜炎的候选基因已经超过5年。此外，进一步的基因型和表型研究表明，这种特殊的突变不仅与典型的视网膜色素变性有关，而且与黄斑变性相关。更多代或仅黄斑变性，提示GCAP2基因突变可能与遗传异质性有关。此外，由于GCAP2蛋白是一种钙结合蛋白，也提示钙离子在视网膜变性发生时可能与GCAP2基因突变有关。关于第二点，即视网膜色素变性的新药物治疗，我们已经报道了钙拮抗剂对RCS大鼠和rd（视网膜变性）小鼠视网膜变性的实验性治疗作用（Takano, Nakazawa, et al.,2004）。这些实验动物研究表明，一些钙拮抗剂可能作为视网膜色素变性的光感受器保护剂发挥作用。我们进一步研究了antocyanine对实验性视网膜变性的影响。结果表明，它具有延缓RCS大鼠视网膜变性的电生理作用。这些结果进一步表明，安东尼花青素可作为色素性视网膜炎的治疗剂。少

The aims of this research project are to investigate responsible genes for hereditary retinal degeneration namely retinitis pigmentosa and to examine the possibility for novel medical treatments for these diseases based on the findings of molecular pathogenesis that would be obtained by the molecular genetic analyzes.As for the first point, i. e. molecular genetic analysis for retinitis pigmentosa and allied diseases, we have first reported that the GCAP2 gene is one of the responsible genes for retinitis pigmentosa based on the findings that we had identified the same mutation in the GCAP2 gene in the affected members of three independent Japanese families (Sato, Nakazawa, et al.,2005). We had focused on this gene as a candidate gene for retinitis pigmentosa for more than 5 years. Moreover, the further genotype-and-phenotype study revealed that this particular mutation was associated with not only typical retinitis pigmentosa, but also retinitis pigmentosa associated with macular dege … More neration or solely macular degeneration, suggesting that the mutation in the GCAP2 gene may be related to genetic heterogeneity. In addition, because GCAP2 protein is a kind of calcium-binding protein, it is also suggested that calcium ion may play a certain role when retinal degeneration occurs in relation to the mutation in the GCAP2 gene.As for the second point, i. e. novel medical treatment for retinitis pigmentosa, we have already reported the experimental therapeutic effects of calcium antagonist on retinal degeneration of RCS rats and rd (retinal degeneration) mouse (Takano, Nakazawa, et al.,2004). These experimental animal studies favorably suggest the possibility that some of calcium antagonists may play as a photoreceptor-protective agents for retinitis pigmentosa. We further examined the effect of antocyanine on experimental retinal degeneration. Results indicate that it delays retinal degeneration of RCS rats electrophsyolosically. These results suggest further availability of antocyanine as a thrapeutic agent for retinitis pigmentosa. Less